Gender-Related Survival Differences Associated With Polymorphic Variants of Estrogen Receptor Beta (ERβ) in Patients with Metastatic Colon Cancer

Estrogen replacement therapy in women has demonstrated a protective effect in the development of colonic carcinomas. Gender-related differences in the development of colonic carcinomas have also been reported. Estrogen receptor beta (ERβ) is expressed in colon carcinomas and has demonstrated prognostic value in colon cancer patients. This study investigated an ERβ 3’ non-coding polymorphism associated with transcriptional activity to determine clinical outcome in patients with metastatic colon cancer. Genomic DNA from 318 metastatic colon cancer patients, 177 males and 141 females, were collected from 1992 to 2003. These patients were analyzed for CA repeat polymorphism of the ERβ gene. Gender-related survival differences were associated with an ERβ (CA)(n) repeat polymorphism (P for interaction=0.003, the likelihood ratio test). Female patients with any short <22 (CA)(n) repeat alleles had shorter overall survival compared to female patients that had both long ≥22 (CA)(n) repeat alleles. In the male patients the opposite overall survival difference was found. This study supports the role of an ERβ (CA)(n) repeat polymorphism as a prognostic marker in metastatic colon cancer; however, this prognostic factor had opposite implications based on gender.